Subcutaneous Ocrelizumab Shows Noninferiority to IV Administration in Relapsing, Primary Progressive MS

Scott Newsome, DO, MSCS, FAAN

According to data from the phase 3 OCARINA II study (NCT05232825) of subcutaneous ocrelizumab (Ocrevus; Genentech) in patients with relapsing or primary progressive multiple sclerosis (MS), the formulation is comparable to its intravenous (IV) counterpart in terms of clinical benefit.¹ The investigators came to this conclusion as the study achieved the primary end point of demonstrating noninferiority of a 920-mg dose of subcutaneous therapy to the 600-mg IV dose.

All told, the subcutaneous and IV administration led to similar exposure overall during the first 12 weeks of treatment for the 116 patients who received each therapy in the study, with a geometric mean ratio comparing both arm’s area under the curve (AUC) of 1.29 (90% CI, 1.23-1.35; subcutaneous AUC weeks 1-12, 3500 µg/mL per day; IV AUC weeks 1-12, 2750 µg/mL per day). Additionally, the geometric mean ratio for the max concentration (Cmax) of 0.96 (90% CI, 0.92-1.01; subcutaneous Cmax, 132 µg/mL; IV Cmax, 137 µg/mL).

The data were presented in a poster by Scott Newsome, DO, MSCS, FAAN, the director of the Stiff Person Syndrome Center and a professor of neurology at Johns Hopkins Medicine, at MSMilan 2023, the joint ECTRIMS-ACTRIMS meeting, held October 11-13, in Milan, Italy. “The selected ocrelizumab subcutaneous 920-mg dose was well-tolerated, and achieved similar levels of B-cell depletion as seen with ocrelizumab IV 600 mg, with no treatment emergent ADAs [antidrug antibodies] to ocrelizumab,” Newsome and colleagues wrote. They added that the “administration of ocrelizumab subcutaneous 920 mg resulted in near-complete suppression of radiological (MRI) and clinical (relapses) disease activity as measured up to week 24,” similar to the IV formulation.

Regarding clinical disease activity, 99% of patients experienced no relapses during the study period up to week 24, with 106 and 105 patients in the subcutaneous and IV groups, respectively, reporting none. Both groups had a single patient report 1 relapse (0.9% of each group), for an unadjusted per year relapse rate of 0.02 for both groups. As for T1 gadolinium-enhancing lesions and T2 lesions, both groups reported similar baseline numbers—the subcutaneous group had 118 and 118, respectively, and the IV group had 118 and 118, respectively. By week 24, the T1 lesion counts were 49 for the subcutaneous group and 52 for the IV group, while T2 lesion counts were 61 and 65 for the 2 patient cohorts, respectively (week 8 adjusted lesion rate, 0.11 for subcutaneous, 0.12 for IV; week 24 adjusted lesion rate, 0.00 for both).

As for safety data, which included 118 patients in each group, the therapies were comparable, though the subcutaneous group did report more adverse events (AEs), with a rate of 73.7% (n = 87) compared with 45.8% (n = 54) in the IV group. Serious AEs were comparable, with the subcutaneous group reporting a rate of 2.5% (n = 3) and the IV group reporting a rate of 3.4% (n = 4). Newsome and colleagues acknowledged that the difference between the groups was driven by nonserious mild and moderate injection reactions, which were deemed nontreatment limiting and resolved on their own, with only a “few patients require[ing] treatment with analgesics and antihistamines.” The most common location injection reactions—which occurred in 54 patients (45.8%)—reported were erythema (29.7%), pain (14.4%), swelling (8.5%), and pruritus (6.8%); and the most common systemic injection reactions—which occurred in 13 patients (11%)—were headache (2.5%) and nausea (1.7%). Notably, none of the AEs led to withdrawal in either group.

“Twice-yearly subcutaneous injection of ocrelizumab, administered in around 10 minutes, could deliver clinical benefit, significantly reduced time and treatment burden, improved resource use, and offered greater flexibility in administration and site of patient care,” Newsome et al wrote.

“We are pleased to share that Ocrevus 10-minute subcutaneous injection suppressed brain lesions as effectively as the intravenous infusion,” Levi Garraway, MD, PhD, the chief medical officer and head of Global Product Development at Genentech, said in a statement.² “Having this additional treatment option may improve the treatment experience for both patients and physicians, and we hope the twice-a-year dosing will offer the same high adherence and persistence.”

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REFERENCES
1. Newsome SD. Subcutaneous Ocrelizumab in Patients With Multiple Sclerosis: Results of the Phase III OCARINA II Study. Presented at: MSMilan; October 11-13, 2023; Milan, Italy. POSTER P370.
2. Genentech’s Ocrevus Twice-Yearly, 10-Minute Subcutaneous Injection Was Non-Inferior to Intravenous Infusion and Provided Near-Complete Suppression of Brain Lesions. Genentech. News release. October 11, 2023. Accessed October 11, 2023. https://www.businesswire.com/news/home/20231010331768/en/Genentech%E2%80%99s-Ocrevus-Twice-Yearly-10-Minute-Subcutaneous-Injection-Was-Non-Inferior-to-Intravenous-Infusion-and-Provided-Near-Complete-Suppression-of-Brain-Lesions